Poliovirus is a member of the picornaviruses, a large family of small ribonucleic acid-containing viruses responsible for many serious human and animal diseases (Rueckert, R. R. Virology, 2nd ed. (Field, B. N. et al., eds.) Raven Press, Ltd., New York, p. 508-548 (1982)). Two genera of the picornavirus family are enteroviruses, which include poliovirus and Coxsackievirus, and rhinoviruses. Poliovirus is the etiologic agent of the disease poliomyelitis in humans, and there are three known serotypes of the virus. The oral poliovaccine, typically given to children, is a mixture of the Sabin strain of the three serotypes of the virus. Mahoney and Leon (the parent strains of Sabin 1 and 3, respectively) are human neurovirulent strains of poliovirus. The oral poliovirus vaccine is safe and effective, yet has two limitations. First, the vaccine is unstable; current vaccines are inactivated by relatively brief (less than 24 hours) exposure to temperatures of 37.degree. C., necessitating transport in a frozen state from the site of manufacture to the locale where they are administered. Second, the vaccine occasionally reverts to virulence in vaccine recipients; the reverted virulent virus may also be passed to other individuals who come into contact with the recipient in whom the vaccine has reverted. The human rhinoviruses consist of at least 100 serotypes and are the primary causative agents of the common cold. Because of the large number of serotypes, development of a vaccine is problematic; antiviral agents may therefore be the best approach to treatment. Other important members of the picornavirus family include human hepatitis A virus, Theiler's murine encephalomyelitis virus, foot-and-mouth disease virus, and mengovirus.
Several crystal structures of poliovirus and rhinovirus capsids have been solved by X-ray diffraction. The X-ray structures of poliovirus P1/Mahoney (Hogle, J. M., et al., Science 229:1358 (1985)); poliovirus P3/Sabin (Filman, D. J., et al., EMBO J. 8:1567 (1989)); rhinovirus 14 (Rossman, M. G., et al., Nature 317:145 (1985)); rhinovirus 1A (Smith, T. J., et al., Science 233:1286 (1986)); and rhinovirus 16 (Oliveira, M. A., et al., Structure 1(1):51-68 (1993)) are strikingly similar, although poliovirus and the rhinoviruses are currently classified in different genuses. From experiment, it is known that there is a binding site in the poliovirus structure which usually binds a lipid-like molecule (Filman, D. J., et al., EMBO J. 8:1567 (1989)). When a drug is bound in this site, the virus is stabilized, and in some cases, infection is prevented (McSharry, J. J., et al., Virology 97:307 (1979); Smith, T. J., et al., Science 233:1286 (1986); reviewed in Zhang, A., et al., Virology, 3:453 (1992)).
The existing drugs against these viruses are only moderately effective. Available drugs are typically effective against a limited subset of the rhinovirus serotypes. In addition, the drugs have either failed to demonstrate sufficient prophylactic effect or are converted in the body into inactive metabolites. Furthermore, current drugs have all been derived from the same parent compound that was found through large-scale random screening of known chemicals for activity against the virus, a very expensive and time-consuming process. A need continues for additional drugs with better efficacy, and with efficacy against several viruses.